The present invention relates to an apparatus for irradiating fluids. More particularly, the present invention concerns an apparatus for permitting cells to be irradiated by an ultraviolet light source.
The transplantation of cells into an allogeneically different recipient has been researched by several medical investigators in an attempt to treat specific medical diseases and disorders. In order to successfully carry out such a transplantation of cells, it is necessary to immunosuppress antigen expression and/or recognition of the transplanted cells. In that way, the body's natural tendency to reject the transplantation of the allogeneic cells can be overcome.
One generally recognized method for immunosuppressing the antigen expression and recognition of the allogeneic cells is to subject the cells to ultraviolet radiation. The uses of ultraviolet radiation within the context of cellular transplantation are discussed in an article authored by H. Joachim Deeg entitled "Ultraviolet Irradiation in Transplantation Biology," Transplantation, Vol. 45, No. 5, pp. 845-851, May 1988.
Several other articles have also been written describing specific methods that have been employed for subjecting transplant cells to ultraviolet radiation. For example, in one method, blood diluted in a phosphate buffer was placed in petri dishes and subjected to ultraviolet light for twenty minutes. The light source emitting the ultraviolet light was positioned at a specified distance from the petri dish. However, not all of the experiments utilizing that method were apparently conducted with the light source positioned at the same distance from the petri dishes. Hardy, M. A., Lau, H. T., Weber, C., Reemtsma, K.: "Pancreatic Islet Transplantation: Immuno-alteration With Ultraviolet Irradiation", World Journal of Surgery, Vol. 8, No. 2, pp. 207-213, April 1984. Hardy, M. A., Lau, H., Reemtsma, K.: "Prolongation of Rat Islet Allografts With the Use of Ultraviolet Irradiation, Without Immunosuppression", Transplantation Proceedings, Vol. 16, No. 3, pp. 865-869, June 1984.
In another method, platelets were suspended in a solution, placed in an open petri dish to a depth of 1.5 mm and subjected to ultraviolet light irradiation while being continuously shaken. Slichter, S. J., Deeg, H. J., Kennedy, M. S.: "Prevention of Platelet Alloimmunization in Dogs With Systemic Cyclosporine and by UV-Irradiation or Cyclosporine-Loading of Donor Platelets", Blood, Vol. 69, No. 2, pp. 414-418, February 1987.
An additional method includes placing whole blood which has been diluted with Waymouth's minimal medium in petri dishes at a layer thickness of 1.5 mm and irradiating the suspension with ultraviolet light for thirty minutes. Deeg, H. J., Aprile, J., Graham, T. C., Appelbaum, F. R., Storb, R.: "Ultraviolet Irradiation of Blood Prevents Transfusion-Induced Sensitization and Marrow Graft Rejection in Dogs", Blood, Vol. 67, No. 2, pp. 537-539, February 1986.
Various other articles have been published in addition to those noted above concerning the use of ultraviolet light irradiation on cells. See, for example, Lindahl-Kiessling, K., Safwenberg, J.: "Inability of UV-Irradiated Lymphocytes to Stimulate Allogeneic Cells in Mixed Lymphocyte Culture", Int. Arch. Allergy, Vol. 41, pp. 670-679, 1971; Balsh, J. D., Francfort, J. W., Perloff, L. J.: "The Influence of Ultraviolet Irradiation on the Blood Transfusion Effect", Surgery, pp. 243-249, August 1985; Lau, H., Reemtsma, K., Hardy, M. A.: "Prolongation of Rat Islet Allograft Survival by Direct Ultraviolet Irradiation of the Graft", Science, Vol. 223, pp. 607-609, Feb. 10, 1984.
It becomes readily apparent from a review of the above articles that the techniques and methods presently employed in ultraviolet light irradiation for transplant and transfusion related procedures suffer from several drawbacks and are susceptible to improvement. In particular, there is no uniformity among the various techniques currently used. In fact, the nature of the techniques is such that even with respect to each individual test, uniformity is difficult to maintain. For example, since the cellular suspension is placed in petri dishes and then subjected to irradiation in the various methods, uniformity can only be maintained if the distance between the cellular suspension and the light source is kept constant. Of course, it is rather evident that such distance depends upon the amount of cellular suspension placed in the petri dish and, clearly, the amount of cellular suspension in a petri dish can be a difficult factor to keep constant. Cells which are placed and suspended in a given volume of solution begin to settle to the bottom of the petri dish over time. Thus, the number of cells in suspension during irradiation tends to decrease throughout the irradiation process.
A related problem that arises when the cellular suspension is irradiated in petri dishes according to the above procedures is that it is difficult to subject all of the cells in the cellular suspension to the same amount of ultraviolet irradiation. That is due in part to the fact that the cellular suspension is somewhat stagnant in the petri dishes. That is to say, the cells in the suspension do not move throughout the suspension but rather, maintain their relative positions within the suspension. As a consequence, cells on the surface of the cellular suspension located closer to the ultraviolet light source are subjected to a different amount of irradiation than underlying cells in the cellular suspension. Although one of the foregoing articles mentions shaking the petri dish during irradiation, that technique would not be entirely effective in overcoming the aforementioned problem.
For example, shaking a petri dish that is not covered in order to subject the cells to movement results in an increase in the amount of evaporation of the cellular suspension. On the other hand, covering the petri dish prior to shaking may not be an effective solution because the material from which the cover is made can affect, and significantly reduce, the amount of irradiation received by the cellular suspension. Thus, a difficult calibration procedure is necessary.
Another drawback associated with the techniques currently employed in ultraviolet light irradiation for transplant/transfusion related procedures is that there is no stability with respect to other factors affecting the irradiation process. For instance, the temperature in the area surrounding the irradiation process can have a significant effect upon the intensity of the irradiation process. Accordingly, if the ambient temperature is not maintained at a particular level, consistent and reliable results will not be possible with respect to successive irradiation processes.
Similarly, during the initial hours of operation, the output from the ultraviolet light source can vary in fluorescent lamp systems. Thus, a cellular suspension irradiated during the initial hours of operation will be subjected to a different amount of irradiation than cellular suspensions that are irradiated later.